The PI proposes studies of the structure, function and genetics of the gonococcal lactoferrin (LF) receptor. Principal questions include the frequency of expression in fresh clinical isolates of the two proteins (LbpB and LbpA) that make up the receptor. We will address whether gonococci expressing the LF receptor are better equipped to attach to eukaryotic cells, and to cause urethral infection in human volunteers. The protein domains in LbpB and LbpA that bind LF will be analyzed, as will the functional contribution of LbpB to the various functions of the LF receptor. We will test whether there is high frequency variation in expression of LbpB, and the genetic basis for frequent deletions in lbpb and lbpa. Antibodies will be raised against LbpB and LbpA to assess the potential of these antigens as components of a vaccine for gonorrhea, and to assist in studies of structure and function of the proteins. The studies are important for better understanding gonococcal pathogenesis and vaccine development, and also other mucosal pathogens including meningococci that infect similar mucosal surfaces and that make comparable receptors.